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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2003

Effects of hindlimb unweighting on the mechanical and structure properties of the rat abdominal aorta

Previous studies have shown that hindlimb unweighting of rats, a model of microgravity, reduces evoked contractile tension of peripheral conduit arteries. It has been hypothesized that this diminished contractile tension is the result of alterations in the mechanical properties of these arteries (e.g., active and passive mechanics). Therefore, the purpose of this study was to determine whether the reduced contractile force of the abdominal aorta from 2-wk hindlimb-unweighted (HU) rats results from a mechanical function deficit resulting from structural vascular alterations or material property changes. Aortas were isolated from control (C) and HU rats, and vasoconstrictor responses to norepinephrine (10(-9)-10(-4) M) and AVP (10(-9)-10(-5) M) were tested in vitro. In a second series of tests, the active and passive Cauchy stress-stretch relations were determined by incrementally increasing the uniaxial displacement of the aortic rings. Maximal Cauchy stress in response to norepinephrine and AVP were less in aortic rings from HU rats. The active Cauchy stress-stretch response indicated that, although maximum stress was lower in aortas from HU rats (C, 8.1 +/- 0.2 kPa; HU, 7.0 +/- 0.4 kPa), it was achieved at a similar hoop stretch. There were also no differences in the passive Cauchy stress-stretch response or the gross vascular morphology (e.g., medial cross-sectional area: C, 0.30 +/- 0.02 mm(2); HU, 0.32 +/- 0.01 mm(2)) between groups and no differences in resting or basal vascular tone at the displacement that elicits peak developed tension between groups (resting tension: C, 1.71 +/- 0.06 g; HU, 1.78 +/- 0.14 g). These results indicate that HU does not alter the functional mechanical properties of conduit arteries. However, the significantly lower active Cauchy stress of aortas from HU rats demonstrates a true contractile deficit in these arteries.

Non-NASA Center↗
NASA NTRS1973

Influence of flow and pressure on wave propagation in the canine aorta.

Data on wave speed acquired from 20 anesthetized dogs showed that the thoracic aorta was essentially nondispersive for small artificially generated pressure waves traveling in the downstream or the upstream direction and having frequencies between 40 and 120 Hz. The amplitude of these waves decayed exponentially with the distance traveled. Theoretical studies are cited which have shown that changes in wave speed due to variations in pressure and flow produce marked nonlinear effects in hemodynamics.

Histand, M. B.↗
NASA NTRS1980

Hydroelastic effects in the aorta bifurcation zone

The mechanical behavior of the vessels and blood is mathematically analyzed at the point of aortic bifurcation using a homogeneous single layer channel as a model of the aorta. Allowance is made for the fact that the aortic intima is considerably less rigid than the other layers. For analysis of blood flow in the major arteries, the blood is treated as a viscous Newtonian fluid whose movements are described by Navier-Stokes equations and a continuity equation. Blood flow dynamics at the aortic bifurcation are discussed on the basis of the results.

Volmir, A. S.↗
NASA NTRS2000

Evidence that simulated microgravity may alter the vascular nonreceptor tyrosine kinase second messenger pathway

Simulated microgravity (hind limb unweighting; HU) reduces maximal contractile capacity to norepinephrine (NE) but not 5-hydroxytryptamine (5-HT) in the rat abdominal aorta of male Wistar rats. Our earlier study showed that voltage-operated calcium channels, the MAPK pathway [1], and vasoconstrictive prostaglandins contribute to the NE-induced contraction of control (C) but not HU, aorta rings. Genistein, a general tyrosine kinase inhibitor, caused a significant reduction in vascular contractility in C but not HU arteries. The present study explored the role of protein kinase C (PKC) and extracellular receptor-activated kinase 1 and 2 (ERK1/2) in the HU-induced vascular hyporesponsiveness to NE. Microgravity was simulated in Wistar rats by 20 day HU. The abdominal aorta was removed from control and HU rats, cut into 3 mm rings, and mounted in tissue baths to measure isometric contraction. Protein levels were determined using Western blot analysis. PD98059, a selective MAPKK inhibitor, caused a marked inhibition of NE-induced contraction in both C and HU arteries. Calphostin C, a PKC inhibitor, completely abolished the contractile response to NE in both C and HU tissues. Phosphorylated (activated) ERK1/2 protein mass was greater in C, compared to HU, aortas, and was reduced by genistein only in C tissues. MAPK total protein levels in the rat aorta were increased in the HU-treated, compared to C, animals. These results indicate that PKC represents an early transduction step in the contractile response to NE in the rat abdominal aorta. That inhibition of the step immediately before activation of MAPK reduced contraction in both C and HU tissues, while general tyrosine kinase inhibition with genistein blocked only the control responses, suggests that a nonreceptor tyrosine kinase may be involved in HU-induced vascular hyporesponsiveness to NE.

Non-NASA Center↗
NASA NTRSDate not supplied

Cardiovascular Responses to Simulated Spaceflight: Molecular Signatures and Surrogate Outputs to Measure CVD Risk

During extended space missions beyond low Earth orbit, astronauts will encounter prolonged periods of weightlessness and low dose space radiation. Previous studies have shown that exposure to small doses of high LET radiation (< 50 cGy) can lead to both short-term and long-term alterations in heart function, structure and underlying molecular mechanisms. In this study, we aim to identify the molecular signature associated with the cardiovascular response to simulated galactic cosmic radiation (5-ion GCR) alone or in combination with simulated weightlessness at time intervals relevant to mission length and recovery. Additionally, we aim to determine whether sex impacts cardiovascular responses to these spaceflight factors. Our overarching goal is to enhance our understanding of the cardiovascular risks associated with extended space missions and the clinical endpoints they suggest. We hypothesize that exposure to simulated space radiation leads to enduring alterations in the transcriptome, redox signaling and cytokine environment of cardiovascular tissue, some which have known links with reduced cardiovascular performance, aging, and increased risk of cardiovascular disease (CVD). Furthermore, we posit that simulated space radiation exposure in combination with simulated microgravity exacerbates cardiovascular deficits compared to single factor exposure. Female and male C57BL/6J mice, aged 23-24 weeks, were exposed to a single dose of 5, 15, or 50 cGy of 5-ion GCR, or sham-treated (0 cGy). Euthanasia was performed at 14 days and ~4 months post-irradiation. Hearts, aorta and blood plasma were collected shortly thereafter. RNA-sequencing of left ventricles at ~4 months post-GCR exposure revealed sex differences in the heart transcriptome with a few genes showing radiation-dependent changes in expression levels. Notably, some of the differentially expressed genes in 15 and 50 cGy GCR groups are known to play roles in the development of CVD. Analysis of protein levels of a subset of inflammatory cytokines in the heart indicated sex differences but no differences between sham and 50 cGy groups. Results also showed correlations among differentially expressed genes and a subset of inflammatory cytokines, with some correlations altered by GCR exposure. These findings suggest that GCR exposure can modify protein and gene networks linked to inflammation and CVD progression. In the aorta, telomere lengths were comparable across treatment groups sexes. Mitochondrial copy number is a biomarker for mitochondrial function with decreased copy numbers associated with cardiometabolic disease traits. Mitochondrial copy numbers of aorta also showed no sex nor dose differences. In a second study, mice underwent one week of simulated microgravity by hindlimb unloading (HU) and then exposed to a single dose of 15 cGy of 5-ion GCR. HU was conducted for an additional two weeks following GCR exposure. Single factor exposure groups (HU or GCR only) also were included in the study. Euthanasia was then performed and the same tissues were collected. Protein levels of select inflammatory cytokines in the heart showed sex-dependent differences in expression. In the aorta, telomere lengths and mitochondrial copy number also showed sex differences. In summary, our results indicate differences between sexes in biomarkers related to cardiovascular health. Exposure to 5-ion GCR or HU, alone or in combination, did not result in changes in most of the cardiovascular biomarkers that were examined. However, in the heart, simulated space radiation at doses of 15 and 50 cGy led to long-term alterations in the expression levels of a small group of genes known to be associated with the progression of CVD. The long-term transcriptomic changes resulting from exposure to simulated space radiation should be carefully investigated to mitigate adverse cardiovascular events during and after deep space missions. Our results also highlight the importance of sex-specific strategies in monitoring and maintaining cardiovascular health during and after deep space missions.

cardiovascular↗
NASA NTRS1976

Cardiovascular function during sustained +G/z/ stress

The development of aerospace systems capable of very high levels of positive vertical accelerators stress has created a need for a better understanding of the cardiovascular responses to acceleration. Using a canine model, the heart and cardiovascular system were instrumented to continuously measure coronary blood flow, cardiac output, left ventricular and aortic root pressure, and oxygen saturation in the aorta, coronary sinus, and right ventricle. The animals were exposed to acceleration profiles up to +6 G, 120 s at peak G; a seatback angle of 45 deg was simulated in some experiments. Radiopaque contrast medium was injected to visualize the left ventricular chamber, coronary vasculature, aorta, and branches of the aorta. The results suggest mechanisms responsible for arrhythmias which may occur, and subendocardial hemorrhage which has been reported in other animals.

Erickson, H. H.↗
NASA NTRS2003

Development of the Aortic Baroreflex in Microgravity

Baroreceptors sense pressure in blood vessels and send this information to the brain. The primary baroreceptors are located in the main blood vessel leaving the heart (the aorta) and in the arteries in the neck (the carotid arteries). The brain uses information from the baroreceptors to determine whether blood pressure should be raised or lowered. These reflex responses are called baroreflexes. Changing position within a gravity field (i.e., moving from lying to sitting or standing) powerfully stimulates the baroreflexes. In weightlessness, the amount of stimuli that the baroreflexes receive is dramatically reduced. If this reduction occurs when the pathways that control the baroreflexes are being formed, it is possible that either the structure or function of the baroreceptors may be permanently changed. To study the effect of microgravity on structural and functional development of the aortic baroreflex system, we studied young rats (eight days old at launch) that flew on the Space Shuttle Columbia for 16 days. Six rats were studied on landing day; another six were studied after re-adapting to Earth's gravity for 30 days. On both landing day and 30 days after landing, we tested the sensitivity of the rats' baroreflex response. While the rats were anaesthetized, we recorded their arterial pressure, heart rate, and aortic nerve activity. After the tissues were preserved with perfusion fixation, we also examined the baroreflex structures. On landing day, we found that, compared to the controls, the flight rats had: fewer unmyelinated nerve fibers in their aortic nerves lower baroreflex sensitivity significantly lower contraction ability and wall tension of the aorta a reduced number of smooth muscle cells in the aorta. In the 30-day recovery group, the sensitivity of the baroreflex showed no difference between the flight rats and the control groups, although the unmyelinated fibers of the aortic nerve remained reduced in the flight rats. The results show that spaceflight does affect the development of the aortic baroreflex. The sensitivity of the reflex may be suppressed; however, the function of the blood pressure control system can re-adapt to Earth's gravity if the rats return before maturation. The structural differences in the input pathway of the reflex (Le., the reduction in nerve fibers) may remain permanently.

Shimizu, Tsuyoshi↗
NASA NTRS1995

'Non-hypotensive' hypovolaemia reduces ascending aortic dimensions in humans

1. The notion that small, 'non-hypotensive' reductions of effective blood volume alter neither arterial pressure nor arterial baroreceptor activity is pervasive in the experimental literature. We tested two hypotheses: (a) that minute arterial pressure and cardiac autonomic outflow changes during hypovolaemia induced by lower body suction in humans are masked by alterations in breathing, and (b) that evidence for arterial baroreflex engagement might be obtained from measurements of thoracic aorta dimensions. 2. In two studies, responses to graded lower body suction at 0 (control), 5, 10, 15, 20 and 40 mmHg were examined in twelve and ten healthy young men, respectively. In the first, arterial pressure (photoplethysmograph), R-R interval, and respiratory sinus arrhythmia amplitude (complex demodulation) were measured during uncontrolled and controlled breathing (constant breathing frequency and tidal volume). In the second, cross-sectional areas of the ascending thoracic aorta were calculated from nuclear magnetic resonance images. 3. Lower body suction with controlled breathing resulted in an increased arterial pulse pressure at mild levels (5-20 mmHg; ANOVA, P < 0.05) and a decreased arterial pulse pressure at moderate levels (40 mmHg; ANOVA, P < 0.05). Both R-R intervals and respiratory sinus arrhythmia were negatively related to lower body suction level, whether group averages (general linear regression, r > 0.92) or individual subjects (orthogonal polynomials, 12 of 12 subjects) were assessed. 4. Aortic pulse area decreased progressively and significantly during mild lower body suction, with 47% of the total decline occurring by 5 mmHg. 5. These results suggest that small reductions of effective blood volume reduce aortic baroreceptive areas and trigger haemodynamic adjustments which are so efficient that alterations in arterial pressure escape detection by conventional means.

NASA Discipline Cardiopulmonary↗
NASA NTRS1974

Changes in mesenteric, renal, and aortic flows with +Gx acceleration

Previous studies in man and dogs have indicated that the splanchnic bed might contribute to the maintenance of arterial pressure during +Gx acceleration. Eight mongrel dogs were chronically instrumented with Doppler flow probes around the superior mesenteric (SMA) and renal arteries (RA) as well as the terminal aorta (TA). A solid-state pressure transducer was placed in the aorta distal to the flow probe. Using alpha-chloralose anesthesia following a 2-4 week recovery period, the animals were subjected to 120 sec at levels of 5, 10 and 15 +Gx acceleration on a 7.6-m radius centrifuge. The results indicate that both an active component and a mechanical component contribute to the maintenance of arterial pressure during +Gx acceleration.

Stone, H. L.↗
NASA NTRS1980

Content of lipids in blood and tissues of animals during hypodynamia

Experiments on 97 rats and 50 rabbits were undertaken to study the influence of hypodynamia on the lipid content in the blood, liver, heart, and in the aorta. Reduction of muscular activity contributed to the increase of cholesterol and beta lipoprotein levels in the blood and to accumulation of cholesterol in the liver and the heart. The total lipid content in these tissues decreased. In the aorta the total lipid content increased, while lecithin and cephalin figures went down. The character of biochemical changes in hypodynamia resembles in many ways the lipid metabolism changes in atherosclerosis.

Federov, I. V.↗
NASA NTRS1980

Effects of hypodynamia on the hemocoagulative properties of the vascular wall and myocardium

The hemocoagulative properties of the aorta (laminar), myocardium, hollow veins, and fibrinolytic capacity of tissues were studied in 14 rabbits subjected to 7 days of restricted mobility and compared to those of 10 control animals. Two tables of results show that, as a result of hypodynamia, the thromboplastic activity of the inner and middle layers of the aorta together with the destruction of endothelium increases the hemocoagulative potential and creates the threat of thrombogenesis. There is also an increase in fibrin-stabilizing activity for all tissues.

Inchina, V. I.↗
NASA NTRS1980

Noninvasive aortic bloodflow by Pulsed Doppler Echocardiography (PDE) compared to cardiac output by the direct Fick procedure

Left ventricular stroke volume was estimated from the systolic velocity integral in the ascending aorta by pulsed Doppler Echocardiography (PDE) and the cross sectional area of the aorta estimated by M mode echocardiography on 15 patients with coronary disease undergoing right catheterization for diagnostic purposes. Cardiac output was calculated from stroke volume and heart volume using the PDE method as well as the Fick procedure for comparison. The mean value for the cardiac output via the PDE method (4.42 L/min) was only 6% lower than for the cardiac output obtained from the Fick procedure (4.69 L/min) and the correlation between the two methods was excellent (r=0.967, p less than .01). The good agreement between the two methods demonstrates that the PDE technique offers a reliable noninvasive alternative for estimating cardiac output, requiring no active cooperation by the subject. It was concluded that the Doppler method is superior to the Fick method in that it provides beat by beat information on cardiac performance.

Source record↗
NASA NTRS1980

Beat by beat stroke volume assessment by PDE in upright and supine exercise

A 3.0 MHz pulse Doppler echocardiograph was used to estimate instantaneous stroke volume and cardiac output in 8 men during steady state supine and upright exercise at 300 kpm/min which were compared with other studies utilizing invasive procedures. The mean transients in heart rate and stroke volume and cardiac output for the first 20 sec of exercise in each posture were then determined. Centerline blood velocities were obtained in the ascending aorta with the transducer positioned manually in the suprasternal notch. Mean supine values for stroke volume and cardiac output at rest and exercise were 111 (6.4) and 112 ml (9.7 L/min), respectively, for supine. The corresponding results for upright were 76 (5.6) and 92 ml (8.4 L/min). These values compare favorably with prior studies. The transient response of cardiac output following the onset of upright was about twice as fast as in S because of the rapid and almost immediate upsurge in stroke volume. In supine, only heart rate served to augment cardiac output as stroke volume initially fell. The faster initial aortic flow in upright must represent the rapid mobilization of pooled venous blood from the leg veins which more than accounts for the additional volume (184 ml) of blood passing through the aorta during upright compared with supine in the first 20 sec.

Source record↗
NASA NTRS1981

Beat-by-beat stroke volume assessment by pulsed Doppler in upright and supine exercise

The instantaneous stroke volume (SV) and cardiac output (Q) in eight male subjects during steady-state supine (S) and upright (U) exercises at 300 kpm/min is assessed by a 3.0-MHz pulsed Doppler echocardiograph. The mean transients in heart rate (HR), SV, and Q for each posture were determined and the center-line blood velocities obtained in the ascending aorta. Results show that the mean supine values for SV and Q at rest and exercise were 111 ml and 6.4 l/min and 112 ml and 9.7 l/min, respectively. The corresponding results for U were 76 ml and 5.6 l/min and 92 ml and 8.4 l/min, respectively. The values compare favorably with previous studies utilizing invasive procedures. The transient response of Q following the onset of exercise in U was about twice as fast as in S because of the rapid and almost immediate upsurge in SV. The faster rise in aortic flow in U with exercise represented and additional volume (184 ml) of blood passing through the aorta compared with S in the first 20 exercises. It is suggested that the rapid mobilization of pooled venous blood from the leg veins during U was responsible for the increased blood flow.

Loeppky, J. A.↗